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The oropharyngeal microbiome, the collective genomes of the community of microorganisms that colonizes the upper respiratory tract, is thought to influence the clinical course of infection by respiratory viruses, including Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the causative agent of Coronavirus Infectious Disease 2019 (COVID-19). In this study, we examined the oropharyngeal microbiome of suspected COVID-19 patients presenting to the Emergency Department and an inpatient COVID-19 unit with symptoms of acute COVID-19. Of 115 initially enrolled patients, 50 had positive molecular testing for COVID-19+ and had symptom duration of 14 days or less. These patients were analyzed further as progression of disease could most likely be attributed to acute COVID-19 and less likely a secondary process. Of these, 38 (76%) went on to require some form of supplemental oxygen support. To identify functional patterns associated with respiratory illness requiring respiratory support, we applied an interpretable random forest classification machine learning pipeline to shotgun metagenomic sequencing data and select clinical covariates. When combined with clinical factors, both species and metabolic pathways abundance-based models were found to be highly predictive of the need for respiratory support (F1-score 0.857 for microbes and 0.821 for functional pathways). To determine biologically meaningful and highly predictive signals in the microbiome, we applied the Stable and Interpretable RUle Set to the output of the models. This analysis revealed that low abundance of two commensal organisms, Prevotella salivae or Veillonella infantium (< 4.2 and 1.7% respectively), and a low abundance of a pathway associated with LPS biosynthesis (< 0.1%) were highly predictive of developing the need for acute respiratory support (82 and 91.4% respectively). These findings suggest that the composition of the oropharyngeal microbiome in COVID-19 patients may play a role in determining who will suffer from severe disease manifestations.
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The shortage of PFF2, N95, and KN95 respirators and their equivalents for the respiratory protection of the population and health professionals during COVID-19 pandemic has driven the adoption of alternative measures to address the lack of personal protective equipment (PPE). The use of surgical masks, handmade masks, and even the prolonged use of respirators were some of the measures adopted in response to the high demand for these products, and their consequent shortage. In this context, the present study evaluated the microbiota and integrity of reused PFF2 respirators in the central sterile services department of a hospital. Respirators that had been used for 0 h, 12 h, 24 h, and 36 h were sampled for the inoculation and cultivation of fungi and bacteria and the identification of their microbiota. To assess the integrity of the respirators, a filtration efficiency assessment test was conducted of the respirators used for 36 h. The results obtained showed that the microbiota of the respirators comprised commensal fungi and bacteria from the oral and nasal regions of human beings. It was also found that after 36 h of use, the respirators did not demonstrate a decrease in filtration efficiency;that is, they retained their 97% filtration efficiency. Considering the findings regarding the presence and pathogenicity of microorganisms, it is possible that the reuse of respirators for up to 36 h does not harm the health of immunocompetent users. In terms of PPE efficiency, no compromises were evidenced.
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Mucormycosis is a fungal infection which has been regrouped under emerging infectious disease. In this COVID-19 pandemic, the incidence of mucormycosis has been reported in many parts of India. Systemic condition that weakens one's immune systems like uncontrolled diabetes, chemotherapy or chronic long-term illness poses a grave threat for this fungal infection. Patients with oral cancer and precancer remain at significant risk for developing severe infections regardless of significant developments in therapy. Few studies have reported that this opportunistic fungal pathogen may be cultured from the oral cavity. Our findings disprove the oral carriage of filamentous fungi (Zygomycetes) among the group of patients with oral squamous cell carcinoma, oral potentially malignant disorders who are susceptible to immunological deficits and healthy subjects. This finding strongly supports that the oral niche of healthy as well as the patients with oral lesions do not harbour this filamentous fungi.
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Dysbiosis, especially in the gut plays a crucial role in the pathogenesis of a wide variety of diseases, including inflammatory bowel disease, colorectal cancer, cardiovascular disease, DDS obesity, diabetes and multiple sclerosis. At mucosal surfaces, mucosal polymeric immunoglobulin A(IgA)antibodies are known to be important to regulate the gut microbiota as well as to exclude infection induced by pathogenic bacteria or virus such as influenza and SARS-CoV-2(severe acute respiratory syndrome coronavirus 2). Since the 1970 s, oral administration of IgA or IgG antibodies has been performed against infectious enteritis caused by pathogenic Escherichia coli or Clostridioides difficile. However, none of them has been successfully developed as an antibody drug up to now. Although IgA is well known to modulate the gut commensal microbiota, the therapeutic IgA drugs to treat dysbiosis has not been developed. Here, we discuss the advantages of therapeutic IgA antibodies.Copyright © 2022, Japan Society of Drug Delivery System. All rights reserved.
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Dysbiosis, especially in the gut plays a crucial role in the pathogenesis of a wide variety of diseases, including inflammatory bowel disease, colorectal cancer, cardiovascular disease, DDS obesity, diabetes and multiple sclerosis. At mucosal surfaces, mucosal polymeric immunoglobulin A(IgA)antibodies are known to be important to regulate the gut microbiota as well as to exclude infection induced by pathogenic bacteria or virus such as influenza and SARS-CoV-2(severe acute respiratory syndrome coronavirus 2). Since the 1970 s, oral administration of IgA or IgG antibodies has been performed against infectious enteritis caused by pathogenic Escherichia coli or Clostridioides difficile. However, none of them has been successfully developed as an antibody drug up to now. Although IgA is well known to modulate the gut commensal microbiota, the therapeutic IgA drugs to treat dysbiosis has not been developed. Here, we discuss the advantages of therapeutic IgA antibodies.Copyright © 2022, Japan Society of Drug Delivery System. All rights reserved.
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INTRODUCTION: E-cigarette or vaping-associated lung injury (EVALI) is an uncommon complication of e-cigarettes or vaping. Most cases are associated with tetrahydrocannabinol (THC) containing products. "Dabbing" refers to the process of ingesting high concentrations of THC-containing oils or waxes with butane solvents to vaporize cannabinoids for inhalation. Another distinction is the presence of impurities and unpurged butane in the vapors inhaled by the users. DESCRIPTION: A 29-year-old male presented with cough, dyspnea, and fever seven days prior to admission. He reported smoking marijuana but denied vaping. Initial chest radiograph demonstrated multifocal pneumonia. PCR for SARS-CoV-2 was negative. He required four liters of supplemental oxygen. Physical exam was remarkable for diffuse pulmonary crackles. Broad spectrum antibiotics for pneumonia were initiated. Oxygen requirements rapidly increased, prompting intubation 48 hours from presentation. Ventilator settings escalated to a positive end-expiratory pressure of 18 cm H2O with 100% FiO2. Computed tomography angiography ruled out pulmonary embolism, however showed diffuse patchy nodular and confluent opacities. Respiratory cultures grew commensal flora and blood cultures were negative. Comprehensive laboratory investigations for an infectious etiology and autoimmune vasculitis were negative. In further discussion with the patient's wife, he has been "dabbing" for the past six months. High dose intravenous steroids were initiated. The patient continued to have refractory hypoxemic and hypercapnic respiratory failure with ARDS requiring prone positioning. The patient ultimately required transition to veno-venous extracorporeal membrane oxygenation (VV-ECMO). The patient received 12 days of VV-ECMO and was eventually liberated after 19 days of ventilator support. At discharge he was asymptomatic, at his baseline level of function, and required no supplemental oxygen. He was discharged on daily steroids with a taper and outpatient follow-up. DISCUSSION: The necessity of VV-ECMO utilization in "dabbing" associated acute lung injury represents a rare severe presentation. Dabbing is emerging as a trend among young adults and represents an under-investigated cause of severe inhalational lung injury.
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Background. Coinfections, both bacterial and viral, occur with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, but prevalence, risk factors, and associated clinical outcomes are not fully understood. Methods. We used the Coronavirus Disease 2019-Associated Hospitalization Surveillance Network (COVID-NET), a population-based surveillance platform to investigate the occurrence of viral and bacterial coinfections among hospitalized adults with laboratory-confirmed SARS-CoV-2 infection during March 2020 and February 2022. Patients receiving additional standard of care (SOC) molecular testing for viral pathogens (14 days prior to admission or 7 days after), including respiratory syncytial virus, rhinovirus/enterovirus (RV/EV), influenza, adenovirus, human metapneumovirus, parainfluenza viruses, and endemic coronaviruses, were included. SOC testing for clinically relevant bacterial pathogens (7 days before admission or 7 days after) from sputum, deep respiratory, and sterile sites were included. The demographic and clinical features of those with and without bacterial infections were compared. Results. Among 2,654 adults hospitalized with COVID-19 and tested for all 7 virus groups, another virus was identified in 3.1% of patients. RV/EV (1.2%) and influenza (0.4%) were the most commonly detected viruses. Half (17,842/35,528, 50.2%) of hospitalized adults with COVID-19 had bacterial cultures taken within 7 days of admission, and 1,092 (6.1%) of these had a clinically relevant bacterial pathogen. A higher percentage of those with a positive culture died compared to those with negative cultures (32.3% vs 13.3%, p< 0.001). Staphylococcus aureus was the most common isolate overall;Pseudomonas aeruginosa was the second most common respiratory isolate This figure includes 1,408 bacterial cultures from 1,066 individuals. Deep respiratory sites include endotracheal aspirate, bronchoalveolar lavage fluid, bronchial washings, pleural fluid, and lung tissue. Commensal organisms were excluded. Conclusion. Consistent with previous studies, a relatively low proportion of adults hospitalized with COVID-19 had concomitantly identified viral or bacterial infections. Identification of a bacterial infection within 7 days of admission is associated with increasedmortality among adults hospitalized with COVID-19. Conclusions about the clinical relevance of bacterial infections is limited by the retrospective nature of this study.
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The mutation of the SARS-CoV-2 virus, which cause person-to-person transmission, is the pivotal reason for the pandemic outbreak in the year 2020. Infection symptoms include fever, dry cough, lethargy, severe pneumonia, respiratory distress syndrome, and death. COVID-19 induces a systemic inflammatory reaction that impairs the immune system, commonly known as cytokine release syndrome. Pro-inflammatory cytokines and chemokines are abundant in COVID-19 sufferers' bodies. COVID-19 has a disproportionate impact on the elderly, both directly and through several comorbidities associated with age. Nutrition is without hesitation, a crucial factor in maintaining good health. Some nutrients are essential for the immune system's health and function, exhibiting synergistic actions in critical immune response steps. Vitamin D, C, and Zinc stand out among these nutrients because they have immunomodulatory properties and help to maintain physical tissue barriers. Considering the viability of the virus, nutrients that boost the immunity henceforth the severity of viral infections declines with improved prognosis become important. As a result, the purpose of this review is to provide a complete outline of vitamins D, C, and zinc's involvement during the immune response towards infection, and to enlighten their commensal action of maintaining physical barriers including integument and mucous membrane. Appropriate vitamin D, C, and zinc consumption may represent a feasible pharmacological intervention during the COVID-19 pandemic due to the high surge in population interaction and the commencement of inflammation. Copyright © 2022, Indian Association of Biomedical Scientists. All rights reserved.
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SESSION TITLE: Critical Diffuse Lung Disease Cases 2 SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: Acute eosinophilic pneumonia (AEP) is dramatic in presentation mimicking infectious pneumonia or acute respiratory distress syndrome in previously healthy individuals. Medications are a commonly recognized cause of AEP. Daptomycin, has been strongly linked to AEP. Herein, we present a case of a patient with a septic joint treated with Daptomycin who went on to develop AEP. CASE PRESENTATION: Patient is an 80 year old man with history of hypertension, hypothyroidism, atrial flutter, complete heart block status post pacemaker, who had a hx of a mucinous cyst on his left index finger, requiring hospitalization. Blood cultures were positive for MRSA s/p debridement of the joint. He was discharged on 4 weeks of intravenous daptomycin. Two weeks after being discharged he presented back to the hospital with fevers, fatigue and worsening shortness of breath. His temperature was 103.8 and O2 saturation of 90% on 2L NC. Laboratory findings included WBC count of 8.6 with no eosinophilia on differential, ESR 110, negative blood cultures, sputum cultures with commensal flora, negative urine legionella, PCR for SARS COV-2 was negative. Chest radiograph showed mild interstitial airspace disease in the left mid and lower thorax, along with small bilateral pleural effusions. CT chest showed scattered bilateral consolidations and ground glass opacities and trace bilateral effusions. Daptomycin was switched to Vancomycin. Patients oxygen requirements had increased to 6l NC. Patient underwent airway exam with bronchoscopy and broncheoalveolar lavage in superior segment of the lingula, which showed inflamed bronchial mucosa with copious secretions. Cell count of the BAL showed increased eosinophil count with negative gram stain and culture. Patient was started on methylprednisolone 60 mg four times per day and then tapered. Vancomycin was switched to oral linezolid. Patient's hypoxia improved and was discharged home on 3l NC. At four week follow up, he no longer required oxygen on ambulation and chest radiograph showed complete resolution of infiltrates. DISCUSSION: Over 140 drugs have been recognized as a cause of drug induced eosinophilic pneumonia (DIEP). The diagnosis of DIEP requires febrile illness <5 days, diffuse bilateral infiltrates, hypoxemia and BAL showing 25% eosinophils or eosinophilic pneumonitis on lung biopsy. Additionally, a diagnosis of DIEP requires exposure to a candidate drug in the appropriate time frame, exclusion of infectious causes of eosinophilic pulmonary opacities. It also requires clinical improvement after cessation of medication. Daptomycin has been strongly linked to DIEP. In 2010 US FDA issued a warning about the risk of developing eosinophilic pneumonia during treatment with Daptomycin. CONCLUSIONS: Daptomycin is strongly linked with DIEP. Clinicians should maintain a high index of suspicion for DIEP in patient treated with daptomycin who develop respiratory distress. Reference #1: Uppal, P., LaPlante, K.L., Gaitanis, M.M. et al. Daptomycin-induced eosinophilic pneumonia - a systematic review. Antimicrob Resist Infect Control 5, 55 (2016). https://doi.org/10.1186/s13756-016-0158-8 Reference #2: Cottin V. Eosinophilic Lung Diseases. Clin Chest Med. 2016 Sep;37(3):535-56. doi: 10.1016/j.ccm.2016.04.015. Epub 2016 Jun 25. PMID: 27514599. Reference #3: Rosenberg CE, Khoury P. Approach to Eosinophilia Presenting With Pulmonary Symptoms. Chest. 2021 Feb;159(2):507-516. doi: 10.1016/j.chest.2020.09.247. Epub 2020 Sep 28. PMID: 33002503;PMCID: PMC8039005. DISCLOSURES: No relevant relationships by Kamelia Albujoq No relevant relationships by Rajaninder Sharma
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SESSION TITLE: COVID-19 Case Report Posters 1 SESSION TYPE: Case Report Posters PRESENTED ON: 10/17/2022 12:15 pm - 01:15 pm INTRODUCTION: We describe the clinical course of a COVID-19 patient with Streptococcus Dysgalactiae (SD) infective endocarditis, managed with six weeks of antibiotics and valve replacement surgery. CASE PRESENTATION: A 50-year-old previously healthy man presented with two weeks of fever, congestion, and diarrhea, and one day of acute change in mentation. On arrival, the patient's heart rate was 130/min, respiratory rate 25/min, and temperature 103.5 F. On physical examination, he appeared lethargic. Initial labs showed a white blood count of 16 k/mm with bands and platelets of 64 k/cmm. The patient was treated empirically for severe sepsis with intravenous vancomycin and cefepime. Blood cultures grew SD. Antibiotics were narrowed to intravenous ceftriaxone. A CAT scan of the chest, abdomen, and pelvis identified multiple splenic infarcts. A transesophageal echocardiogram was performed to evaluate the potential source of the splenic emboli, and this showed mild to moderate mitral regurgitation and a large globular mobile vegetation on the anterior mitral valve. Intravenous gentamicin was added to the treatment regimen. Subsequent cultures remained negative, and he underwent bioprosthetic mitral valve replacement on hospital day 11. He received a total of 6 weeks of outpatient intravenous antibiotic therapy. DISCUSSION: SD is a normal commensal of the skin, upper airway, and gastrointestinal tract. It can cause localized and invasive infections. Major risk factors for invasive infections include malignancy, diabetes mellites, and other cardiovascular diseases. Besides a recent COVID-19 infection, our patient was healthy. The COVID-19 infection causes a hypercoagulable state, and when combined with COVID-19 related diarrhea, can lead to the translocation of the gut bacteria, and subsequent infective endocarditis (IE) [1]. SD is a rare cause of IE, but the incidence of IE in bacteremic patients is about 10% [2]. Clinicians should have a low threshold to suspect IE in cases of SD bacteremia. American Heart Association Guidelines on IE [3] state that systemic embolization occurs in 22% to 50% of cases of IE, and the highest incidence of embolism occurs when the vegetation is mobile, on the anterior mitral valve and > 10 mm, like in our case. In such patients, early cardiac surgery should be considered. SD bacteremia recurrence occurs in about 10% of patients within the first year, and patients should be informed about this risk. CONCLUSIONS: Clinicians should suspect IE in the setting of SD bacteremia. COVID-19 infection increases the chances of the development of infective endocarditis. Prolonged intravenous antibiotic therapy and prompt replacement of the involved valve is necessary. SD IE is associated with a high rate of recurrence, and clinicians should be cognizant of this risk. Reference #1: "COVID-19 INFECTION PREDISPOSING ENDOCARDITIS ….” https://www.scienceopen.com/document?vid=02f2bbbe-479d-4d11-ad60-2ceba336a4e1. Accessed 4 Apr. 2022. Reference #2: "Bacteremia caused by group G Streptococci, taiwan - PubMed.” https://pubmed.ncbi.nlm.nih.gov/18439377/. Accessed 4 Apr. 2022. Reference #3: "Clinical relevance of vegetation localization by … - Semantic Scholar.” https://www.semanticscholar.org/paper/Clinical-relevance-of-vegetation-localization-by-in-Rohmann-Erbel/0106e26e3f2102eb6dd2fd7e086210c0a44ebf45. Accessed 4 Apr. 2022. DISCLOSURES: No relevant relationships by Husam Bader No relevant relationships by Poorva Bhide No relevant relationships by Gaurav Mohan No relevant relationships by Muhammad Tayyeb No relevant relationships by Charmee Vyas No relevant relationships by Siva Naga Yarrarapu
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The origins of preexisting SARS-CoV-2 cross-reactive antibodies and their potential impacts on vaccine efficacy have not been fully clarified. In this study, we demonstrated that S2 was the prevailing target of the preexisting S protein cross-reactive antibodies in both healthy human and SPF mice. A dominant antibody epitope was identified on the connector domain of S2 (1147-SFKEELDKYFKNHT-1160, P144), which could be recognized by preexisting antibodies in both human and mouse. Through metagenomic sequencing and fecal bacteria transplant, we demonstrated that the generation of S2 cross-reactive antibodies was associated with commensal gut bacteria. Furthermore, six P144 reactive monoclonal antibodies were isolated from naïve SPF mice and were proven to cross-react with commensal gut bacteria collected from both human and mouse. A variety of cross-reactive microbial proteins were identified using LC-MS, of which E. coli derived HSP60 and HSP70 proteins were confirmed to be able to bind to one of the isolated monoclonal antibodies. Mice with high levels of preexisting S2 cross-reactive antibodies mounted higher S protein specific binding antibodies, especially against S2, after being immunized with a SARS-CoV-2 S DNA vaccine. Similarly, we found that levels of preexisting S2 and P144-specific antibodies correlated positively with RBD binding antibody titers after two doses of inactivated SARS-CoV-2 vaccination in human. Collectively, our study revealed an alternative origin of preexisting S2-targeted antibodies and disclosed a previously neglected aspect of the impact of gut microbiota on host anti-SARS-CoV-2 immunity.
Subject(s)
COVID-19 , Gastrointestinal Microbiome , Viral Vaccines , Animals , Antibodies, Monoclonal , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Vaccines , Escherichia coli , Humans , Mice , SARS-CoV-2ABSTRACT
Introduction: Postmenopausal women with recurrent urinary tract infections (RUTI) are repeatedly exposed to antibiotics and therefore at risk for colonization by multi-drug resistant organisms. Methenamine hippurate (MH) is FDAapproved for the prevention of RUTI;however, the mechanism of action of MH or, more specifically, the role of MH in the alteration of the urobiome is not known. Since preliminary data has shown that MH may be effective against some bacteria (e.g., Escherichia coli), but not others (e.g., Enterococcus faecalis), we hypothesize that resident bladder microbiota will be altered by administration of MH. Objective: Our objective is to determine the longitudinal effect of MH on the urobiome of postmenopausal women with RUTI. Methods: A longitudinal study with a convenient sample of 10 postmenopausal women with a clinical history of RUTI was conducted (Figure 1). UDI6 questionnaires, voided urine, catheterized urine, and peri-urethral swabs were obtained at baseline and three months after daily MH use. Expanded quantitative urine culture (EQUC) was performed on these specimens. In addition, during the 3-month timeframe, four self-collection windows were completed (windows A-D): (A) prior to initiating MH (baseline urobiome), (B) one week after starting MH, (C) two weeks before the 3-month follow-up, and (D) one week before the 3-month follow-up. Voided urine and peri-urethral swabs were collected daily for one week during windows A-D to determine how the urobiome changed. Sequencing of samples from these collection windows is pending. Results: Ten participants enrolled;however, three participants were not able to complete the study due to allergic reaction, improper handling of samples, and COVID infection. Six participants have completed the study;microbiological studies for one participant are still in process. There were no episodes of acute cystitis for any participant during the length of the study. UDI6 results suggested a trend towards a decrease in frequency, leakage with urgency, and abdominal pain;however, none of these were statistically significant (Table 1). Of the six remaining participants, the average baseline urine pH was 5.8 ± 0.8. For the completed participants, an initial microbiological comparison of EQUC results at baseline and 3-month visits show differences in sample diversity. Specifically, the number of species detected (richness) in catheterized urine increased for all but one participant (Figures 2A and 2B) though there was little or no changes in overall diversity (Shannon Index, Figure 2B) or evenness (Pielou's Index, Figure 2C) for any sample type. Exposure to MH did not result in the loss of uropathogenic species present in catheterized urine at baseline;instead, additional uropathogenic and commensal microbiota were detected at the 3-month visit. Conclusions: UDI6 trended towards symptom improvement in frequency, urge incontinence, and pain, consistent with RUTI prevention and symptoms control. Microbiological results suggest that MH increases the richness of the bladder urobiome. This consistent trend suggests MH may reduce RUTI events by altering the urobiome community richness instead of eliminating uropathogenic microbiota from the bladder. Further studies are needed to understand the interaction between MH and a host that is susceptible to uropathogen overgrowth (Table Presented).
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Introduction: Gut dysbiosis is associated with immune dysfunction and severity in COVID- 191-2. This study aimed to determine targeting dysbiosis as a therapy and its effect on antibody formation, gut dysbiosis and immune profile in patients with COVID-19. Material & Methods: In an open-label study, 25 consecutive hospitalized patients with COVID- 19 received a novel microbiome immunity formula (SIM01) for 28 days;30 patients who did not receive the intervention acted as controls. We collected fecal and blood samples at baseline and week 5 and followed subjects from admission up to five weeks. We performed multi-omics analysis using data from peripheral blood mononuclear cell (PBMC) transcriptome, fecal metagenomic sequencing and fecal metabolomic profiling (Figure 1A). Results: Significantly more COVID-19 patients on SIM01 developed anti-SARS-CoV-2 IgG than the control group at 2 weeks (Figure 1B). Patients on SIM01 (but not controls) showed a significant reduction of plasma levels of interleukin (IL)-6, macrophage colony-stimulating factor (M-CSF), tumour necrosis factor (TNF-a), IL-1RA (Figure 1C) and downregulated COVID-19 related signalling pathway in PBMC at Week 5. Fecal samples of subjects on SIM01 were enriched in commensal bacteria and reduced in opportunistic pathogens at week 4 and 5. Elevated plasma acetic acid in SIM01 group showed a negative correlation with SARS-CoV-2 viral load in nasopharyngeal samples (Figure 2A). Increased relative abundance of Bifidobacteria adolescentis and Coprococcus comes in fecal samples in SIM01 group positively correlated with plasma acetic acid levels (Figure 2B). Conclusion: We showed for the first time a novel microbiome formula SIM01 was effective in hastening antibody formation against SARS-CoV-2, reduced pro-inflammatory immune markers and restored gut dysbiosis in hospitalised COVID-19 patients. References: 1. Zuo T, Zhang F, Lui GCY, et al. Alterations in gut microbiota of patients with COVID-19 during time of hospitalization. Gastroenterology 2020;159:944-955 e8. 2. Yeoh YK, Zuo T, Lui GC, et al. Gut microbiota composition reflects disease severity and dysfunctional immune responses in patients with COVID- 19. Gut 2021;70:698-706. (Figure Presented) (Figure Presented)
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Problem: The placenta performs various functions of the lung/GI/GU tract for the developing fetus, while also moderating host defenses of the fetus against infections in utero, and likely educates the developing fetal immune system. It thus has long-term impacts on the health of both the woman and the child. Knowledge is limited about the underlying mechanisms that enable the placenta to serve as a protective barrier for the fetus against infection. The long-term goals of my research program are to, 1) elucidate the normal barriers to infection in the placenta and show how dysfunction in barrier function can lead to adverse maternal-fetal outcomes, 2) define how viral infections impact placental biology, and 3) characterize possible functional roles for the newly described microbiota at the maternal-fetal interface. Method of Study: To address the above questions, our research includes the use human placentas, primary human trophoblasts and immune cells derived from term placentas, cultured placental cells, trophoblast organoids, and mousemodels. Results: We found that placentas from women who gave birth prematurely exhibit reduced autophagy activity. Prematurity and reduced autophagy levels were also strongly associated with maternal infection. In a mouse model of pregnancy, we showed that placentas from mice deficient for Atg16L1 were significantly less able to withstand infection, and the deficient mice gave birth prematurely upon an inflammatory stimulus. We have also shown that the autophagy pathway plays a key role in ZIKV vertical transmission from mother to fetus. We demonstrated that hydroxychloroquine (HCQ), an autophagy inhibitor approved for use in pregnant women, can attenuate placental and fetal ZIKV infection and ameliorate adverse placental and fetal outcomes. More recently, we have identified a small molecule inhibitor that targets the NS2B-NS3 protease of ZIKV and inhibits viral replication. It has recently become evident that SARS-CoV-2 infection is also associated with adverse outcomes for pregnant women, including preterm birth, preeclampsia, and fetal growth restriction. We localized SARS-CoV-2 to the placenta and showed that infection alters the Renin Angiotensin System (RAS) that regulates blood pressure, thereby increasing risk for preeclampsia. In new work, we are showing that SARS-CoV-2 non-structural proteins affect autophagy in different ways than in Zika virus. Finally, we have discovered that the maternal fetal interface of the placenta harbors intracellular resident microbes, and functionally demonstrated that they do not induce any inflammatory response or cell death but may promote immune tolerance and support normal pregnancy outcomes. Conclusions: For the past 10 years of my career, I have been working on host microbial interactions at the maternal fetal interface. Our work has led to new insights into viral infections, showing how they co-opt host defenses, and that tolerance may have microbial drivers. We have shown how cellular pathways in the placenta such as autophagy and RAS mechanistically regulate host defenses against pathogens, including ZIKV and SARS-CoV-2. Additionally, our studies provide a foundation for understanding possible 'commensal' microbial- placental interactions and hint at the functional importance of microbes at the fetal maternal interface in maintaining placental health and supporting fetal development.
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Purpose/Background: In the US, intestinal spirochetosis (IS) as a cause of infectious colitis has mainly been described in the HIV positive population. This case describes IS in an HIV negative, COVID positive patient suggesting the need for a broader differential of chronic diarrhea in the COVID era. Hypothesis/Aim: To increase awareness of the need for a potentially broader differential of chronic diarrhea in the COVID era. Methods/Interventions: This is a case study describing an association between COVID and intestinal spirochetosis. Results/Outcome(s): Spirochetes, gram negative spiral-shaped flagellated bacteria, are best known for their ability to cause systemic disease in the form of Syphilis and Lyme Disease, but the genus Brachyspiraceae (Brachyspira aalborgi, Brachyspira pilosicoli) has also been described as both a commensal organism and an invasive pathogen causing intestinal spirochetosis (IS). IS in the US has largely been described in the MSM HIV population as a colitis presenting with abdominal pain and persistent diarrhea secondary to epithelial invasion with destruction of the intestinal brush border leading to malabsorption. IS remains an important part of the work up of infectious colitis in this population. In this case study, IS was diagnosed in an HIV negative, COVID positive patient whose COVID diagnosis coincided with the symptomatic presentation of IS suggesting that it is important to include IS in the differential diagnosis of chronic diarrhea in the COVID population regardless of HIV status. In this study, a 60 yo HIV negative MSM presented with abdominal pain x 3 weeks followed by persistent watery diarrhea refractory to imodium. No history of recent travel. No known infectious contacts. Prior colonoscopy 9 years prior to presentation WNL. After one episode of hematochezia, CT abd/pelvis was performed demonstrating colitis and COVID-related changes to the lung bases. Testing confirmed COVID infection, which was self-limited. Initial work up for infectious colitis was negative for gonorrhea, chlamydia, HIV, HSV, O+P, and C. Difficile. Colonoscopy was performed revealing no evidence of gross colitis. Histopathology demonstrated microscopic colitis w/ spirochete colonization of the intestinal epithelium (image 1). A course of metronidazole led to resolution of symptoms. Limitations: This is a descriptive study describing an association, but it does not imply causation. Conclusions/Discussion: Intestinal spirochetosis has been described as a cause of abdominal pain and refractory diarrhea in the US mainly in an immunosuppressed, HIV positive population. This case describes symptomatic intestinal spirochetosis in an HIV negative, COVID positive patient who hitherto COVID diagnosis had no risk factors for immunosuppression suggesting a link between COVID and IS. Further review is necessary to establish a true association, but this case suggests that IS should be considered during the work up of chronic diarrhea in COVID positive patients. (Figure Presented).
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Nucleated erythroid cells (NEC) are the precursors of the most massive population of human cells – erythrocytes, for which functions of hemo- and immunoregulation have been shown at various stages of ontogenesis and in various organs and tissues of the human body. NEC perform this function by secreting cytokine proteins, growth factors, enzymes such as arginase-2, ROS, and by surface molecules PD-L1 and PD-L2. Their important regulatory role has been shown for the formation of fetoplacental immunosuppression, immunosuppression during pregnancy, suppression of the response against commensals in the gastrointestinal tract, in the pathogenesis of bacterial and viral infections in adults, in the pathogenesis of tumor growth and autoimmune diseases, as well as participation in the recognition of pathogen-associated molecular patterns using Toll-like receptors in fish and birds. Such qualities, together with their number and width of distribution, represent NEC as active participants in hemo- and immunoregulation, which makes it important to study their regulatory role in health and disease.
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Introduction: The invasion of lung tissue by a commensal like aspergillus after severe viral infection has been known.[1] But coronavirus has multiple fangs like immune dysfunction, precipitates new onset diabetes and hypercoagulability.[2] We hereby present a case of long COVID with pulmonary aspergillosis and deep vein thrombosis (DVT). Case Study: A 46 year old male presented with one and half month history of fever, cough with expectoration, hemoptysis. He had tested positive for COVID and diabetes two months before and had required intensive care treatment. The Chest Xray [Figure 1a] showed left upper lobe opacity. Chest CT Scan [Figure 2] showed cavity with central hypodense component within anterior segment of left upper lobe (bird's nest appearance). BAL from that segment grew aspergillus. The patient was started on voriconazole, hemoptysis was controlled and subsequently discharged. But 15 days later, he was readmitted with hemoptysis and left side calf pain and swelling. Lower limb venous doppler showed thrombosis of parts of Left Superficial femoral vein and popliteal vein. CTPA (CT Pulmonary Angiography) didn't show any filling defect. Patient was started on anticoagulation. After 8 weeks patient improved with significant clearing of lung lesion on chest X Ray [Figure 1b]. Discussion: Studies from Wuhan, China, reported secondary fungal infections in 35.3% critically ill patients.[3] Our patient, apart from other risk factors had received corticosteroids and the dose was more than 0.3 mg/kg/d and the duration was upto 4 weeks.[4] Conclusion: Post COVID cases with hemoptysis should be investigated properly considering the multiple pathogenic pathways that are implicated by this virus.
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Most antibodies produced in the body are of the IgA class. The dominant cell population producing them are plasma cells within the lamina propria of the gastrointestinal tract, but many IgA-producing cells are also found in the airways, within mammary tissues, the urogenital tract and inside the bone marrow. Most IgA antibodies are transported into the lumen by epithelial cells as part of the mucosal secretions, but they are also present in serum and other body fluids. A large part of the commensal microbiota in the gut is covered with IgA antibodies, and it has been demonstrated that this plays a role in maintaining a healthy balance between the host and the bacteria. However, IgA antibodies also play important roles in neutralizing pathogens in the gastrointestinal tract and the upper airways. The distinction between the two roles of IgA - protective and balance-maintaining - not only has implications on function but also on how the production is regulated. Here, we discuss these issues with a special focus on gut and airways.
Subject(s)
Friends , Immunoglobulin A , Humans , Immunity, Mucosal , Intestinal Mucosa , Mucous Membrane , Plasma CellsABSTRACT
We conducted two studies to investigate how restaurant advertisements depicting different types of eating scenarios (commensal vs. solitary dining) might influence consumers’ expectations of and attitudes toward the foods and restaurants after they were reminded of the pandemic. Participants expected that the foods shown in the advertisements of commensal dining would be more palatable and likable than the same foods depicted in the advertisements of solitary dining. They also showed more positive attitudes toward both the restaurants and foods. The enhanced hedonic expectations induced by the advertisements depicting commensal dining, however, were modulated by the priming for COVID-19 salience. Collectively, these findings suggest that consumers’ preference for commensal dining can be extended to the advertisements depicting such eating scenarios, but this effect could be attenuated by consumers’ awareness of the pandemic. These findings provide insight into restaurant advertisement design and highlight the negative effect of the pandemic on consumers.